| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Bufarenogin targets the intrinsic apoptosis pathway, specifically through the cooperation of Bax and the adenine nucleotide translocator (ANT). The compound promotes the mitochondrial translocation of Bax, a pro-apoptotic protein, and facilitates its interaction with ANT. This leads to the permeabilization of the mitochondrial outer membrane, release of cytochrome c into the cytoplasm, and activation of the caspase cascade, resulting in apoptosis. Bufarenogin also targets Na⁺/K⁺-ATPase, inhibiting its activity, which may contribute to its cytotoxic effects. The compound may also inhibit receptor tyrosine kinase-regulated signaling pathways, contributing to its antitumor activity. Bufarenogin's effects on cancer stem cells include downregulation of Sox2, reducing the population of cancer stem cells implicated in tumor recurrence and drug resistance.
|
|---|---|
| ln Vitro |
Bufarenogin suppressed the proliferation and metastasis of orthotopical CRC cells by inducing intrinsic apoptosis with the help of Bax and adenine-nucleotide translocator[1].
In vitro, bufarenogin suppresses the proliferation and metastasis of orthotopic colorectal cancer (CRC) cells by inducing intrinsic apoptosis. The compound causes cell death via apoptosis, as demonstrated by mitochondrial translocation of Bax and cytoplasm release of cytochrome c in HCT116 wild-type cells. Bufarenogin exhibits cytotoxicity against HepG2 (human hepatoma) and MCF-7 (human breast cancer) cells. The compound also inhibits the growth and metastasis of CRC cells in vitro, suggesting potential for the treatment of metastatic cancer. Bufarenogin's effects on cancer stem cells include reducing the population of cells expressing stem cell markers, which may contribute to its antitumor activity. The compound's in vitro activities are dose-dependent and have been characterized in multiple cancer cell lines. |
| ln Vivo |
In vivo, bufarenogin has demonstrated potent therapeutic effects in xenografted human hepatoma without notable side effects, at least partially through inhibiting receptor tyrosine kinase-regulated signaling. The compound inhibits metastasis and growth of orthotopic CRC cells in animal models. Bufarenogin treatment leads to reduced tumor growth, decreased metastasis, and improved survival in treated animals. The compound is well-tolerated at therapeutic doses, with no significant weight loss or organ toxicity observed. Bufarenogin's in vivo efficacy supports its potential as an anticancer agent, although further studies are needed to fully characterize its pharmacological profile.
|
| Enzyme Assay |
In vitro enzyme assays for bufarenogin involve assessing its effects on Na⁺/K⁺-ATPase activity. The assay uses purified Na⁺/K⁺-ATPase enzyme and measures the hydrolysis of ATP in the presence of varying concentrations of bufarenogin. The release of inorganic phosphate (Pi) is measured using a colorimetric method, and the IC50 for Na⁺/K⁺-ATPase inhibition is determined. For apoptosis pathway studies, the compound's effects on Bax translocation and cytochrome c release are assessed. Cells are treated with bufarenogin, and mitochondrial and cytoplasmic fractions are prepared. Bax and cytochrome c levels are assessed by Western blotting. Caspase-3/7 activity is measured using fluorogenic substrates.
|
| Cell Assay |
In vitro cell-based assays for bufarenogin are performed using various cancer cell lines, including HCT116 (colon cancer), HepG2 (hepatoma), and MCF-7 (breast cancer). Cells are seeded in 96-well plates and treated with serial dilutions of bufarenogin (typically 0.1-50 μM) for 24-72 hours. Cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays to determine the IC50. Apoptosis is evaluated by flow cytometry using Annexin V/PI staining or by detecting caspase-3/7 activity. Mitochondrial membrane potential is assessed using JC-1 dye. Cell migration and invasion are assessed using transwell or scratch wound assays. The effects on cancer stem cell populations are assessed by flow cytometry using stem cell markers.
|
| Animal Protocol |
In vivo animal studies with bufarenogin are conducted in mouse models of colorectal cancer or hepatoma. Immunodeficient mice are implanted with human tumor cells orthotopically or subcutaneously. Bufarenogin is administered intraperitoneally or orally at doses ranging from 1 to 50 mg/kg. Tumor growth is monitored by imaging or caliper measurements. Metastasis is assessed by examining distant organs for tumor colonies. Survival is monitored. At study termination, tumors are collected for histopathological analysis, immunohistochemistry (e.g., Ki-67 for proliferation, TUNEL for apoptosis), and pharmacodynamic analysis of apoptosis markers (Bax, cytochrome c, caspases). Body weight and clinical signs are monitored to assess tolerability.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of bufarenogin have not been extensively characterized. As a bufadienolide, the compound is expected to have moderate lipophilicity. The compound's absorption, distribution, metabolism, and excretion would need to be determined experimentally. Bufarenogin is typically dissolved in DMSO and formulated in appropriate vehicles for in vivo administration. The compound's stability in biological fluids and its tissue distribution are not well-characterized. For research use, bufarenogin is stored at -20°C and protected from light.
|
| Toxicity/Toxicokinetics |
Bufarenogin is generally well-tolerated at therapeutic doses, with no notable side effects observed in animal studies. The compound has shown a favorable toxicity profile in xenograft models, with no significant weight loss or organ toxicity. No specific toxicological studies have been published in detail. As a research chemical, standard safety precautions should be followed when handling bufarenogin. The compound is for research use only and not for human or veterinary applications. Further toxicological studies are needed to fully characterize the safety profile of bufarenogin for potential clinical development.
|
| References | |
| Additional Infomation |
Bufarenogin is a bufadienolide, a class of compounds found in the venom of toads, which have been studied for their cardiotonic and anticancer activities. Bufadienolides are known to inhibit Na⁺/K⁺-ATPase, an enzyme that plays a critical role in maintaining cellular ion homeostasis. The inhibition of Na⁺/K⁺-ATPase by bufadienolides leads to increased intracellular calcium, which can trigger apoptosis in cancer cells. Bufarenogin's ability to induce apoptosis through the Bax/ANT pathway and inhibit metastasis makes it a promising candidate for anticancer research. The compound's effects on cancer stem cells also suggest potential for preventing tumor recurrence and drug resistance. Bufarenogin is available from chemical suppliers for research purposes.
|
| Molecular Formula |
C24H32O6
|
|---|---|
| Molecular Weight |
416.51
|
| Exact Mass |
416.22
|
| CAS # |
17008-65-0
|
| PubChem CID |
167607
|
| Appearance |
White to off-white solid powder
|
| Density |
1.35g/cm3
|
| Boiling Point |
635.849°C at 760 mmHg
|
| Flash Point |
218.725°C
|
| LogP |
2.391
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
30
|
| Complexity |
847
|
| Defined Atom Stereocenter Count |
9
|
| SMILES |
C[C@]12CC[C@@H](C[C@H]1CC[C@@H]3[C@@H]2C(=O)[C@H]([C@]4([C@@]3(CC[C@@H]4C5=COC(=O)C=C5)O)C)O)O
|
| InChi Key |
SOGONHOGEFLVPE-PUVOGLICSA-N
|
| InChi Code |
InChI=1S/C24H32O6/c1-22-9-7-15(25)11-14(22)4-5-17-19(22)20(27)21(28)23(2)16(8-10-24(17,23)29)13-3-6-18(26)30-12-13/h3,6,12,14-17,19,21,25,28-29H,4-5,7-11H2,1-2H3/t14-,15+,16-,17-,19-,21-,22+,23+,24+/m1/s1
|
| Chemical Name |
5-[(3S,5R,8R,9S,10S,12S,13S,14S,17R)-3,12,14-trihydroxy-10,13-dimethyl-11-oxo-2,3,4,5,6,7,8,9,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]pyran-2-one
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4009 mL | 12.0045 mL | 24.0090 mL | |
| 5 mM | 0.4802 mL | 2.4009 mL | 4.8018 mL | |
| 10 mM | 0.2401 mL | 1.2005 mL | 2.4009 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
